The antibody response to antigen is heterogeneous in both the number of variable regions and constant regions that are produced by the clonal progeny of B cells. The extent of variable region diversity is being studied by examining natural murine antibodies to the phosphorylcholine antigen. Homogeneous antibodies are produced by hybrid cells derived from the fusion of normal antibody-producing cells and myeloma cells. The variable regions of heavy and light chains are determined by amino acid sequencing. Several immunoglobulin heavy chain classes (IgM, IgG, IgA, etc.) can be produced by the clonal progeny of a B cell after antigen stimulation. The relationship between the class of the immunoglobulin on the membrane of B cells and the class of immunoglobulin that is secreted by their clonal progeny will be studied. Cells are separated according to membrane immunoglobulin class using a fluorescence-activated cell sorter. Separated cells are stimulated with antigen in vitro, and the class of secreted antibody is compared to the surface immunoglobulin.